Reversible phosphorylation is an important and common mechanism for regulating many functions in brain including electrical excitation and the consolidation of memory. Much is known concerning the identity and regulation of protein kinases that participate in these processes, but far less is known about the protein phosphatases that are the obligate partners of kinases in signal transduction. Our long-term goal is to understand the function and regulation of Ser/Thr protein phosphatase 5 in the central nervous system. We recently purified this enzyme as a lipid-activated enzyme from brain. Although little is known about the biological function of protein phosphatase 5, studies in non-neuronal cells have implicated this enzyme in hormone signaling pathways controlling gene expression, ion channel regulation and other processes that are central to the function of neurons. In order to understand the role of this enzyme in brain, we plan to identify its cellular targets in neurons and endocrine cells. In addition, we will define signaling pathways in which protein phosphatase 5 participates in brain to further our understanding of how hormones and neurotransmitters control neuronal function.